USPTO Patents Application 09933717

'MAR. 23. 2004

2:38PM

CROUIELL & MORING LLP

NO. 245

U.S. Patent No. 09/933,717

In The Claims :
Please amend tlie claims as follows;

1 , (Currently Amended) An activator Activators - f or a402 nicotinic
acetylcholine receptors containin g, as active ingredient^a heterocyclic c ompound
compounds represented by tho following formula (I):

A is o ptionally - aubi3titutod - a og yl r- grQup; or option ally ou bstitutod
hotorocyclic - grwp a phenyl group which is optionally substituted o ne or more
times bv Ci-Ga alkvl group, halogen atom, nitro group or cyano group: or a J
heterocyclic group selected from the group consisting of thiophene. furan, pyran t
pyrrole. pvrazole* pyridine, pvrimidine, pyrazine. pyridazine. imidazo le, oxazole.
isoxazole. thiazole. isothiazole fc quinoline. isoauinoline> azain dole and
tetrahvdropvrimidine group, which is optionally substituted on e or more times
bv Ci-n 4 alkvl group, or halogen atom ;

wherein:

3£4s-e xygon atom; - sulfur atom; - carbon at o m ; o r - mtrogon atom; -

the dotted line shows either thejpresence or absence of ajbond;

n is Hfrtogor of 1 or 2; and

¥4%

2

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U.S. Patent No. 09/933,717

(j^QHfe hc caoo of X io oxygon atom, group YXio CH 3-GS5 O or GH 3-
GHs-GHs-O-r

(3) in tho caco of X ia sulfur atom, group -Y-X io C HQEt*) CHa S ,

C(R^)"C(R^ - S - or G^g-Q^Q^-S^m whichrR\^ a -^d^ arc hydro g ear-atomy

€4-6 4 alkyl grot^ -e- i - optionally p ubotitutod phonyl group); -

( - 3) - in the caco of X ia - carbonKitem^group Y X io CR srGSsrGS^r'

€H=^ 4 >-Gffi^)^€^^r-GS^^ N"C(B ^- CH = CH (inwhi ehy

R^^-afid^^ aro hydrogen atom; al ky l group; optionally oubstitutod

phonyl group; halogen atom; or ni4a?o - group); an d?

( 4 ) in tho - sE b s e^ f-X is nitrogon - a - t es% the group -Y-X- is— GHa-GHa NH ,

^gg^GHs-GHs-NH-y -CH=C(R8)-N= or -CH==C(R9)-CH=N- (in which, R 8 and R*
ore hydrogen atom; or optionally subatitutod phenyl group which is optionally
substituted one or more times bv Ci-Cd alkvl group, halogen atom, nitro group, or
cvano group ):

or pharmaceutically acceptable salts thereo f - aa active iagrodioa fc.

2. (Currently Amended) fTho activators A composition comprising
an activator for a4(J2 nicotinic acetylcholine receptors according to claim 1,
wherein said activator is an agonist or modulator activator s arc agonists - or
modulators at a4p2 nicotinic acetylcholine receptors.

3

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U.S. Patent No. 09/933J17

3. (Currently Amended) A therapeutic agent for preventing or
treating cerebral circulation diseases comprising an effective amount of the
activator for a4(J2 nicotinic acetylcholine receptors claimed in claim 1 or 2.

4. (Currently Amended) A therapeutic agent for ^ e evonting or
treating neurodegenerative disease, dementia, motor ataxia, and neuropathy and
mental disease comprising an effective amount of the activator for ct4|}2 nicotinic
acetylcholine receptors claimed in claim 1 or 2.

5. (Original) The therapeutic agent according to claim 4, wherein
said neurodegenerative disease is Alzheimer's disease or Parkinson's disease,
said dementia is cerebrovascular dementia, said motor ataxia is Tourette's
syndrome, and said neuropathy and mental disease is neurosis during chronic
cerebral infarction stage, anxiety or schizophrenia.

6. (Currently Amended) A medicament for improving the cerebral
metabolism, neurotransmission functional disorder and memory disorder, for
protecting brain, or having analgesic effect, which comprises an effect ive amount
of the activator for <x4p2 nicotinic acetylcholine receptors claimed in claim 1 or 2.

4

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NO. 245 P. 7

U.S. Patent No. 09/933,717

7. (Currently Amended) A medicament for provonting or treating
inflammatory intestinal diseases comprising an effective amount of the activator
for a4p2 nicotinic acetylcholine receptors claimed in claim 1 or 2.

8. (Currently Amended) A method of activating a4p2 nicotinic
acetylcholine receptors comprising administering a n effectiv e amount of a4p2
nicotinic acetylcholine activating offcotivo amount - af - a compound as claimed in
claim 1 or pharmaceutical^ acceptable salts thereof.

9. (Cancelled)

10. (Currently Amended) An activator A otwatorg-f or a4|32 nicotinic
acetylcholine receptors containing one or more compounds compound claimed in
claim 9 claim IS or pharmaceutical^ acceptable salts thereof as active
ingredient,

1 1 . (Currently Amended) Jih^- Qati - vntorr; A composition comprising
an activator f or a4(J2 nicotinic acetylcholine receptors according to claim 10,
wherein said activator is an agonist or modulatQr- aotivatog& - aro - agonists or
faeduiafeera at a4p2 nicotinic acetylcholine receptors,

5

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NO. 245 P. 8

U.S. Patent No. 09/933,717

12. (Currently Amended) A composition tkorapouti e-ftge&t for
preventing or treating cerebral circulation diseases comprising an effective
amount of t he activator for a4(J2 nicotinic acetylcholine receptors claimed in
claim 10 or 11.

1 3. (Currently Amended) A composition t herapeutic ag e nt for
preventing or treating neurodegenerative disease, dementia, motor ataxia, and
neuropathy and mental disease comprising an effectiv e amount of the activator
for a4|52 nicotinic acetylcholine receptors claimed in claim 10 or 11.

14. (Currently Amended) The composition therapeutic agent
according to claim 13, wherein said neuro degenerative disease is Alzheimer's
disease or Parkinson's disease, said dementia is cerebrovascular dementia, said
motor ataxia is Tourette f s syndrome, and said neuropathy and mental disease is
neurosis during chronic cerebral infarction stage, anxiety or schizophrenia.

15. (Currently Amended) A medicament for improving the cerebral
metabolism, neurotransmission functional disorder and memory disorder, for
protecting the brain, or having analgesic effect , which comprises comprising an
effective amount of t he activator for ot4p2 nicotinic acetylcholine receptors
claimed in claim 10 or 11.

6

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MAR. 23. 2004 2:39PM CROWELL 8c MORING LLP

NO. 245 P. 9

U.S. Patent No. 09/933,717

16. (Currently Amended) A medicament for ppevesttiag-ef treating
inflammatory intestinal diseases comprising an effective amount of t he activator
for ot4p2 nicotinic acetylcholine receptors claimed in claim 10 or 11.

17. (Currently Amended) A method of activating a4(J2 nicotinic
acetylcholine receptors comprising administering a n effective amount of cc4p2
nicotinic acetylcholine aetiv ating - offootivo amount of a compound as claimed in
claim 18 e l aioa r O or pharmaceutical^ acceptable salts thereof.

18. (New) A compound selected from the group consisting of:

1- (6-chloro-S-pyridyi) methyl-2-imino-5-phenyl-l,2-dihydropyrimidine;

2- amino-l-(2~chloro-5-thiazolyl) methylimidazole;
2-amino-l-(6-chloro-3-pyridyl)methyl-4, 5-dimethylimidazole;
2-amino-l-(5-pyrimidyl)methylmidazole;
2-amino-l-(6-chloro-3-p3n:idyl)methyl-4-methylimidazole;
2-amino-l-(6,6 -dichloro-3-pyridyl)methyHmidazole;

2- amino- 1 - (3 -pyridyl) methylimidazole;

2 - amino- 1 - (6 - methyl- 3 -pyridyl) me thylimidazo le ;

2 - amino- 1 - (4 - chlor ob enzyl)imidazole ; and

2- amino- 1 - (7 - az a - 3 -indolyl) me thy limi dazole ;

or a pharmaceutical^ acceptable salt thereof.

7

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